CN102337327A - 28-gene array detection system for breast cancer prognosis - Google Patents
28-gene array detection system for breast cancer prognosis Download PDFInfo
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- CN102337327A CN102337327A CN2010102324469A CN201010232446A CN102337327A CN 102337327 A CN102337327 A CN 102337327A CN 2010102324469 A CN2010102324469 A CN 2010102324469A CN 201010232446 A CN201010232446 A CN 201010232446A CN 102337327 A CN102337327 A CN 102337327A
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Abstract
The invention relates to a 28-gene array detection system for breast cancer prognosis. The detection system is realized by the steps of: collecting a specific breast cancer patient sample, extracting RNA (ribonucleic acid) from the sample, conducting specific amplification to mRNA of a target gene by means of a real-time quantitative RT-PCR (reverse transcription-polymerase chain reaction) technology, then carrying out computer software analysis, thus reading out detection results of the 28 genes. Employing the accurate and rapid real-time quantitative RT-PCR technology, the system of the invention can specifically amplify an even degraded mRNA fragment of the target gene, and can treat and analyze the results with a unique weighted algorithm, as well as can effectively eliminate cases of false positive and false negative.
Description
Technical field
The present invention relates to a kind of Prognosis in Breast Cancer 28 gene array detection systems.
Background technology
Cancer affects 1/3 population in the world.Mammary cancer then is the highest malignant tumour of women's sickness rate, and the whole world has 1,200,000 women illiteracy to suffer from breast cancer every year approximately, and simultaneously, 500,000 people die from mammary cancer.China is one of fastest-rising country of breast cancer incidence; The statistical figure that anticancer association of country announces show; Breast cancer has accounted for 32% of women's malignant tumour in recent years, jumps to the fastest-rising cancer of mortality ratio in the city, can be in any more with metropolitan sickness rate such as Beijing, Shanghai, Guangzhou especially.
In Shanghai, 1972, the sickness rate of women with breast cancer was that per 100,000 philtrums have 17 people; 1992, rising to per 100,000 philtrums had 34 people; 2000, rising to per 100,000 philtrums rapidly had 56.2 people; 2008. rising to per 100,000 philtrums rapidly has 62.5 people.Statistics shows: from 1992～2000 short 8 in the period of, surpassed the ascensional range in 1972～1992 years 20 years.Beijing was since 1978, and mammary cancer also becomes the highest malignant tumour of women's sickness rate, also rose in the speed with annual 2.4% in recent years, and sickness rate has also reached per 100,000 philtrums now has 54 people.In brief, Chinese main cities over 10 years breast cancer incidence increased by 37%, mortality ratio has increased by 38.9%, the rural area mortality ratio has more increased by 39.7%.
The number of the infected peak period of west mammary cancer is 50～55 years old, and along with the growth at women's age, sickness rate is also high more.The mammary cancer age of onset of Chinese women is littler about 10 years old than west women.Obviously, early diagnosis and personalized effective treatment to mammary cancer have extremely important global meaning.
Although the mechanism of tumor invasion is unclear as yet, expression level is unusual due to associated gene mutation or other environmental factorss, is that the basic reason of carcinogenic transformation is widely accepted.The sudden change of cancer gene and abnormal expression just can occur when many early stage malignant tumours.And early stage malignant tumour is realized molecular diagnosis; Be with the revolutionary character leap of histological observation as the existing pathology analytical procedure of main diagnosis basis; The somatotype that not only can confirm various tumours with make a definite diagnosis; And can be according to the biology characteristics of each patient's tumor, predict its following PD and guiding clinical treatment scheme in view of the above.Therefore, foundation is rapid, effective, and the molecular diagnosis of reliable, inexpensive tumor marker learns a skill, and is the main direction of current oncotherapy.
In February, 2007; Drugs approved by FDA Norway Agendia Co., the Mamma Print that 70 genetic expressions are measured to Prognosis in Breast Cancer of Ltd listing, this product is based on the gene chip hybridization technology; Therefore very high to the RNA specification of quality of sample, can only extract RNA with flesh tissue.In addition, this product requires to cost an arm and a leg also than higher to the processing of sample and signal reading out device, and because the hybridization complex disposal process, pollutes easily and produces false positive, thereby be difficult to accomplish extensive popularization clinically.
In recent years, American National tumor center has subsidized a plurality of large-scale experiments.Wherein, The Oncotype DX of California, USA Genomic Health Inc company carries out the detection of genetic expression to mammary cancer patient's postoperative tumor tissues, owing to used the real-time quantitative PCR technology; RNA to tissue preserves requirement reduction greatly; Can from the tumor tissues behind formalin fixed even the paraffin embedding, measure corresponding target gene, and formulate personalized early treatment scheme, achieve success with this.
But Oncotype DX only stresses the recurrence of mammary cancer and the prognosis of transfer are assessed, and failing provides any tutorial message for patient's with high relapse and metastasis risk chemotherapy.Mamma Print is then because the complicacy of technology platform and higher relatively false positive rate.And the both costs an arm and a leg, and once check needs 4000 U.S. dollars above thereby be difficult to effectively promote clinically in China.
Summary of the invention
Technical problem to be solved by this invention is to provide a kind of Prognosis in Breast Cancer 28 gene array detection systems, to solve the defective of above-mentioned prior art.The present invention adopts precisely real-time quantitative RT-PCR technology fast, can carry out specificity to the target gene mRNA fragment after complete or the degraded and amplify; And, can get rid of false positive and false negative effectively to the weighting algorithm Treatment Analysis that the result carries out uniqueness.
Said Prognosis in Breast Cancer 28 gene array detection systems; At first through collecting specific mammary cancer patient's sample; Extract RNA wherein; Further adopt the real-time quantitative RT-PCR technology that target gene mRNA fragment is carried out specificity then and amplify,, can read the detected result of 28 genes through computer software analysis.
Said 28 genes are specific as follows:
A. cell proliferation related because of Ki67, STK15 (serine/threonine kinase-15), Survivin,
CCNB1(cell periodic protein B 1),
MYBL2(myeloblastemia virulence factor 2).
B. growth factor genes involved: GRB7 (growth factor receptor binding protein precursor 7), HER2 (human epidermal growth factor acceptor 2).
C. oestrogenic hormon genes involved: ER (ERs); PGR (PgR); BCL2, SCUBE2 (Signal peptide-CUB-epidermal growth factor-like domain-containing protein 2, signal peptide CUB Urogastron similar structures territory comprises albumen 2).
D. tumor metastasis related gene: MMP11 (matrix metalloproteinase-11), CTSL2 (cathepsin L 2).
E. tumor drug resistance genes involved: MDR-1 (multidrug resistance albumen 1); SPARC (acidity is rich in the Gelucystine secreted protein); BCRP (mammary cancer drug-resistant protein); MRP2 (MRP 2), MLH1 (mismatch repair gene 1), PTEN (Phosphatase and tensin homolog deleted on chromosome ten).
F. tumor susceptibility and other marker gene: GSTM1 (glutathione S-transferase M1), CD68 (differentiation family 68), BAG1 (Bcl-2 combines anti-apoptotic genes expression 1)
G. house-keeping gene: UBC (ubiquitin binding enzyme), GAPDH (glyceraldehyde-3-phosphate dehydrogenase), HPRT1 (hypoxanthine phosphoribosyltransferase 1), RPLPO (ribosomal protein gene), GUS (changeing the beta-Glucuronidase gene), TFRC (transferrin receptor genes).
The present invention adopts real-time quantitative RT-PCR that the measuring result of above-mentioned 28 genes is carried out following calculating and obtained corresponding venture analysis index.
At first the geometric mean by the real-time quantitative RT-PCR value (Ct value) of house-keeping gene obtains background Ct value, and the net value of all the other target gene expression levels (Nvalue) is obtained by formula:
Net value (Nvalue)=background Ct value-target gene Ct value
Get the average expression values (Mean) of the average net value of 2-5 hole replicate measurement as this gene, each gene-correlation score (Score) is all calculated with the average expression values of this gene.
1) cell proliferation related method of calculation because of score value (Score): (a * Ki67+b * STK15+c * Survivin+d * CCNB1+e * MYBL2)/5, wherein a-e is the weighting coefficient of each gene, and span can be from any numerical value of 0.1-10 separately.
2) method of calculation of growth factor genes involved score value (Score):
A * GRB7+b * HER2, a and the b weighting coefficient of two genes of respectively doing for oneself wherein, value can be from any numerical value between the 0.1-10 separately for it.
3) method of calculation of oestrogenic hormon genes involved score value (Score):
-a * ER-b * PGR+c * BCL2-d * SCUBE2, the a-c heterogeneic weighting coefficient of respectively doing for oneself wherein, its span is any numerical value of 0.1 to 10.
4) method of calculation of tumor metastasis related gene score value (Score):
(a * MMP11+b * CTSL2)/2 is the a-b heterogeneic weighting coefficient of respectively doing for oneself wherein, and its span is any numerical value of 0.1 to 10.
5) method of calculation of tumor drug resistance genes involved score value (Score): (a * MDR-1-b * SPARC+c * BCRP+d * MRP2-e * MLH1-f * PTEN)/6; The a-f heterogeneic weighting coefficient of respectively doing for oneself wherein, its span is any numerical value of 0.1 to 10.
6) method of calculation of tumor susceptibility and other marker gene score values (Score):
(its span is any numerical value of 0.1 to 10 for a * GSTM1+b * CD68+c * BAG1)/3, the a-c heterogeneic weighting coefficient of respectively doing for oneself wherein.
7) method of calculation of CAF (endoxan-Zorubicin-Fluracil mixture, cyclophosphamide, Adriamycin and 5-fluorouracil) resistance score value (Score):
A * MDR-1+b * BCRP+c * MRP2-d * PTEN, the a-d heterogeneic weighting coefficient of respectively doing for oneself wherein, its span is any numerical value of 0.1 to 10.
8) method of calculation of aggregative index:
-1 (a * cell proliferation branch+b * growth factor branch+c * ERs branch+d * transfer be correlated with branch+e * tumor susceptibility branch) * f; The a-e heterogeneic weighting coefficient of respectively doing for oneself wherein; Its span is any numerical value of 0.1 to 10; F is an increment coefficient, but any round values in its span 1-1000 scope.
9) recurrence index: definition F is the recurrence index threshold, and its span is 10-1000, like aggregative index＞F, and recurrence index=F; Otherwise equal aggregative index.
10) comprehensive resistance index: definition R is the resistance index threshold, and its span is-1 to+10, like resistance branch＜R, and then comprehensive resistance index=R, otherwise equal the resistance branch.
11) CAF resistance index: definition Rcaf is a CAF resistance index threshold, and its span is-1 to+10, like CAF resistance branch＜Rcaf, and CAF resistance index=Rcaf then, otherwise equal CAF resistance branch.
The expression of said 28 genes in mammary cancer patient tumor tissues is used for the long-term prognosis prediction to the mammary cancer postoperative patient.
The application of said estrogen receptor positive in the wettability mammary cancer patient's who does not occur lymphatic metastasis as yet prognosis prediction.
Said tumor drug resistance related gene expression carries out tumor chemotherapeutic drug resistance Application in Prediction for above-mentioned mammary cancer patient.
In the described tumor chemotherapeutic drug with multidrug resistance albumen 1MDR-1 in the resistance Application in Prediction of expressing relevant tumor chemotherapeutic drug.
Be rich in Gelucystine secreted protein SPARC in the resistance Application in Prediction of expressing relevant tumor chemotherapeutic drug with acidity in the said tumor chemotherapeutic drug.
In the said tumor chemotherapeutic drug with mammary cancer drug-resistant protein BCRP in the resistance Application in Prediction of expressing relevant tumor chemotherapeutic drug.
In the said tumor chemotherapeutic drug with MRP 2MRP2 in the resistance Application in Prediction of expressing relevant tumor chemotherapeutic drug.
In the said tumor chemotherapeutic drug with mismatch repair gene 1MLH1 in the resistance Application in Prediction of expressing relevant tumor chemotherapeutic drug.
In the said tumor chemotherapeutic drug with the resistance Application in Prediction of PTEN at the relevant tumor chemotherapeutic drug of unconventionality expression.
Described tumor chemotherapeutic drug includes but not limited to mustargen, endoxan cyclophosphamide, thio-tepa, lomustine, Myelosan, Dacarbazine, procarbazine.
Described tumor chemotherapeutic drug includes but not limited to Rheumatrex, Ro 2-9757, difuradin, cytosine arabinoside, azathioprine, light basic urea.
Described tumor chemotherapeutic drug includes but not limited to bleomycin, gengshengmeisu, Plicamycin, zhengdingmeisu, Zorubicin Adriamycin, ametycin, dactinomycin.
Described tumor chemotherapeutic drug includes but not limited to vincristine(VCR) vinblastine, NSC-757., harringtonine, NSC 94600, Indirubin, Podophyllum emodi var chinense ethylidene two, taxol taxol.
Described tumor chemotherapeutic drug includes but not limited to cis-platinum, nvelbine, and plug is for group.
Described tumor chemotherapeutic drug comprises the drug combination of the said medicine of claim 12-16.
Said 28 gene array detection systems are refered in particular to the level detection of 28 gene products.
Described gene product comprises the expression level that detects its mRNA with quantifying PCR method.
Described quantifying PCR method is the mammary cancer postoperative flesh tissue with patient, tissue and paraffin-embedded tissue after Superlysoform or other stationary liquids are fixing.
Described quantifying PCR method comprises the expression of the house-keeping gene of quantitative PCR detection is obtained the estimation of whole genetic expression background with geometric mean, is used for the correction to other target gene expression levels.
Described quantitative PCT method comprises that each gene selects many methods of primer is improved simultaneously detection sensitivity and safety for use.
Said prognosis prediction adopts the integrated risk index, and the recurrence exponential calculates the recurrence prognosis of estimating patient.
Described resistance prediction is adopted the resistance exponential of the specific chemotherapy regimen of comprehensive resistance exponential sum to calculate and is estimated the resistance of patient to chemotherapy.
Described particular medication resistance exponential calculates the resistance prediction that includes but not limited to for the CAF Combination chemotherapy.
Compared with prior art, Prognosis in Breast Cancer 28 gene array detection systems of the present invention have following innovative point:
1. the prognosis of breast cancer estimation that has China women characteristic: because different ethnic groups have the different gene background, therefore aspect the prognosis of tumour, the genetic expression of different ethnic groups is composed different.At present, two prognosis of breast cancer diagnostic methods of aforementioned external comparative maturity all are to develop with the patient's sample on the artificial basis of non-China.Therefore, China's breast cancer patient needs the prognosis estimating system that is fit to national women's genetic background badly.The present invention is that sample population is carried out gene profile analysis and weighting assessment with Chinese breast cancer patient, has uniqueness.
2. the genetic expression statistical method of low deviation: target gene expression is being carried out must its qPCR result with the interior house-keeping gene expression level of tumour, being proofreaied and correct as confidential reference items when quantitative with real-time quantitative RT-PCR (qPCR) technology.Most of existing method all is to use simple arithmetical mean, after the expression of some house-keeping genes is handled, obtains a MV, again the expression of target gene level is done normalization method and handle, and the genetic expression value after obtaining proofreading and correct.Recently there are some researches show that the house-keeping gene expression level that arithmetical mean obtains receives the interference ratio of different tissues and various factors bigger, thereby cause correction very mistake to occur last expression of target gene level; This patent uses geometric average method that normalizing is carried out in confidential reference items genetic expression, and this method can significantly reduce the random fluctuation of the expression amount of house-keeping gene, thereby improves the estimation accuracy to the target gene level.
3. the height that guidance can be provided to regimen is the tumor prognosis methods of marking accurately: the present invention predicts the resistance of mammary cancer chemotherapy according to including 6 tumor drug resistance Expression of Related Genes levels; The relevant gene of the general resistance of pair chemotherapeutics is wherein not only arranged, also have the drug-fast characterizing gene of certain based chemotherapy medicine.Therefore, the present invention not only can assess tumor proliferation speed and transfer and relapse risk that mammary cancer reflected, and can assess the drug-resistant intensity and the suitable chemotherapeutics of choice of tumour to chemotherapeutics.
Embodiment
Below in conjunction with specific embodiment technical scheme of the present invention is described in further detail, but embodiment does not limit protection scope of the present invention.
Embodiment 1
Liu XX, woman, 53 years old.Left breast is partly excised, and tumour is wettability, size: 3 * 7 * 5 centimeters, and no lymphatic metastasis, ERs detects positive.
RNA extracts: patient's postoperative sample is taken from the paraffin embedding material of place hospital pathology department, and the tissue about 3 cubic millimeters is inserted the 1.5ml centrifuge tube, and built-in 200 μ l TRIzol (Gibco BRL) mix post-heating to 65 ℃, put then 1 minute on ice.Add 10 μ g E.coli tRNA and 20 μ l Chloroform, incubated at room is 3 minutes behind the abundant mixing.This sample with centrifugal 15 minutes of 4 ℃ of desk centrifuges after, get 100 μ l supernatants and go to another sky centrifuge tube, add 100 μ l isoproponal incubated at room after 10 minutes, 12,000 rev/mins 4 ℃ are centrifugal 10 minutes.With after 100 μ l, the 75% alcohol washing, vacuum-drying 5 minutes adds 50 microlitre double distilled waters with sedimentary RNA.
Real-time quantitative RT-PCR: get 10 μ l; Contain the above-mentioned RNA sample of 1 μ g and add in 384 orifice plates, amplify with ABI PRISM 7900 Sequence Detection System (Perkin-Elmer-Applied Biosystems) or other similar real-time quantitative PCR appearance.It is right that this 384 orifice plate also includes the different primers that produce the tame supporting real-time quantitative RT-PCR reaction soln mixture that provides and correspond to 28 genes.The operation of instrument is carried out according to the parameter of producing family's recommendation, and reads through the data of supporting computer software completion real-time quantitative PCR.
Real-time quantitative PCR to above-mentioned 28 gene gained results with analyze referring to table 1.
At first the geometric mean by the quantitative PCR value (Ct value) of house-keeping gene obtains background Ct value.The net value of all the other target gene expression levels (Nvalue) is obtained by formula:
Net value (Nvalue)=background Ct value-target gene Ct value
Get the average expression values (Mean) of the net value of two hole replicate measurements as this gene, each gene-correlation score is all calculated with the average expression values of this gene.
Cell proliferation related method of calculation: (Ki67+STK15+Survivin+CCNB1+MYBL2)/5 because of score value (Score)
The method of calculation of growth factor genes involved score value (Score): 1.56 * GRB7+0.44 * HER2
The method of calculation of oestrogenic hormon genes involved score value (Score) :-0.8 * ER-1.2PGR+BCL2-SCUBE2
The method of calculation of tumor metastasis related gene score value (Score): (MMP11+CTSL2)/2
The method of calculation of tumor drug resistance genes involved score value (Score): (MDR-1-SPARC+BCRP+MRP2-MLH1-PTEN)/6
The method of calculation of tumor susceptibility and other marker gene score values (Score): (GSTM1+CD68+BAG1)/3
CAF (endoxan-Zorubicin-Fluracil mixture, cyclophosphamide, Adriamycin and 5-fluorouracil) resistance is divided method of calculation: 2 * MDR-1+BCRP+MRP2-PTEN
Aggregative index method of calculation :-1 (relevant+0.83 * tumor susceptibility branch that divides of 1.75 * cell proliferation branch+growth factor branch+ERs branch+1.37 * transfer) x500
The recurrence index: like aggregative index＞500, recurrence index=500, otherwise equal aggregative index.
Comprehensive resistance index: like resistance branch＜0, then comprehensive resistance index=0, otherwise equal the resistance branch.
CAF resistance index: like CAF resistance branch＜0, CAF resistance index=0 then, otherwise equal CAF resistance branch.
Table 1
According to 28 gene test results of this patient, its recurrence index is 117.85, and comprehensive resistance index is 1.1276, is 4.73 for the resistance index of a most frequently used line mammary cancer chemotherapy regimen CAF.According to the judgement criteria of table 2, visible this patient has the risk of recurrence of height, therefore need carry out chemotherapy.This patient is for CAF chemotherapy regimen extreme resistance, but its comprehensive resistance index still belongs to the moderate resistance, therefore should consider to adopt the chemotherapy regimen of other non-CAF combinations.
Table 2
| The recurrence index | Comprehensive resistance index | CAF resistance index | |
| Low | ＞＝500 | ＜0.5 | ＜0.25 |
| Moderate | 150-500 | 0.5-1.5 | 0.25-3.75 |
| Highly | ＜150 | ＞1.5 | ＞3.75 |
Embodiment 2
Wu, the woman, 62 years old, right breast was partly excised, because tumour is less, did not relate to outside the lactiferous ducts, whether therefore failed to confirm wettability. size: 0.5 * 1 * 3.5 centimeters, no lymphatic metastasis, ERs detects the positive.Sample rna extracts with real-time quantitative RT-PCR and operates with embodiment 1.
Real-time quantitative RT-PCR to above-mentioned 28 gene gained results referring to table 3.This patient's recurrence index is 500, and comprehensive resistance index is 0, and CAF treatment resistance index is 0.According to table 2, this patient's mammary cancer belongs to low risk of recurrence, and is extremely sensitive to chemotherapy, and the doctor can select will not chemotherapy perhaps to treat with CAF conventional chemotherapy scheme after the operation.
Table 3
Should be noted that at last; Above embodiment is only unrestricted in order to technical scheme of the present invention to be described; Although with reference to preferred embodiment the present invention is specified, those of ordinary skill in the art should be appreciated that and can make amendment or be equal to replacement the technical scheme of invention; And not breaking away from the spirit and the scope of technical scheme of the present invention, it all should be encompassed in the claim scope of the present invention.
Claims (25)
1. Prognosis in Breast Cancer 28 gene array detection systems; It is characterized in that; Through collecting specific mammary cancer patient's sample, extract RNA wherein, further adopt the real-time quantitative RT-PCR technology that target gene mRNA is carried out specificity then and amplify; Through computer software analysis, can read the detected result of 28 genes.
2. detection system according to claim 1 is characterized in that, said 28 genes are following:
A. cell proliferation related because of Ki67, serine/threonine kinase-15STK15, Survivin, cell periodic protein B 1 CCNB1, myeloblastemia virulence factor 2MYBL2;
B. growth factor genes involved: growth factor receptor binding protein precursor 7GRB7, human epidermal growth factor acceptor 2HER2;
C. oestrogenic hormon genes involved: ERs ER, PgR PGR, BCL2, signal peptide CUB Urogastron similar structures territory comprises albumen 2SCUBE2;
D. tumor metastasis related gene: matrix metalloproteinase-11 MMP11, the 2CTSL2 of cathepsin L;
E. tumor drug resistance genes involved: multidrug resistance albumen 1MDR-1, acidity is rich in Gelucystine secreted protein SPARC, mammary cancer drug-resistant protein BCRP, MRP 2MRP2, mismatch repair gene 1MLH1, PTEN;
F. tumor susceptibility and other marker gene: glutathione S-transferase M1 GSTM1, the differentiation 68CD68 of family, Bcl-2 combines anti-apoptotic genes expression 1BAG1;
G. house-keeping gene: ubiquitin binding enzyme UBC, glyceraldehyde-3-phosphate dehydrogenase GAPDH, hypoxanthine phosphoribosyltransferase 1HPRT1, ribosomal protein gene RPLPO changes beta-Glucuronidase gene GUS, transferrin receptor genes TFRC.
3. the expression of said 28 genes in mammary cancer patient tumor tissues is to the long-term prognosis Application in Prediction of mammary cancer postoperative patient.
4. the application in wettability mammary cancer patient's the prognosis prediction of lymphatic metastasis does not appear in said estrogen receptor positive as yet.
5. said tumor drug resistance related gene expression carries out tumor chemotherapeutic drug resistance Application in Prediction for the said mammary cancer patient of claim 3.
In the described tumor chemotherapeutic drug of claim 5 with multidrug resistance albumen 1MDR-1 in the resistance Application in Prediction of expressing relevant tumor chemotherapeutic drug.
7. be rich in Gelucystine secreted protein SPARC in the resistance Application in Prediction of expressing relevant tumor chemotherapeutic drug with acidity in the described tumor chemotherapeutic drug of claim 5.
In the described tumor chemotherapeutic drug of claim 5 with mammary cancer drug-resistant protein BCRP in the resistance Application in Prediction of expressing relevant tumor chemotherapeutic drug.
In the described tumor chemotherapeutic drug of claim 5 with MRP 2MRP2 in the resistance Application in Prediction of expressing relevant tumor chemotherapeutic drug.
In the described tumor chemotherapeutic drug of claim 5 with mismatch repair gene 1MLH1 in the resistance Application in Prediction of expressing relevant tumor chemotherapeutic drug.
11. in the described tumor chemotherapeutic drug of claim 5 with the resistance Application in Prediction of PTEN at the relevant tumor chemotherapeutic drug of unconventionality expression.
12. each described tumor chemotherapeutic drug of claim 6-11 includes but not limited to mustargen, endoxan cyclophosphamide, thio-tepa, lomustine, Myelosan, Dacarbazine, procarbazine.
13. each described tumor chemotherapeutic drug of claim 6-11 includes but not limited to Rheumatrex, Ro 2-9757, difuradin, cytosine arabinoside, azathioprine, light basic urea.
14. each described tumor chemotherapeutic drug of claim 6-11 includes but not limited to bleomycin, gengshengmeisu, Plicamycin, zhengdingmeisu, Zorubicin Adriamycin, ametycin, dactinomycin.
15. each described tumor chemotherapeutic drug of claim 6-11 includes but not limited to vincristine(VCR) vinblastine, NSC-757., harringtonine, NSC 94600, Indirubin, Podophyllum emodi var chinense ethylidene two, taxol taxol.
16. each described tumor chemotherapeutic drug of claim 6-11 includes but not limited to cis-platinum, nvelbine, and plug is for group.
17. each described tumor chemotherapeutic drug of claim 6-11 comprises the drug combination of the said medicine of claim 12-16.
18. the described 28 gene array detection systems of claim 1 are refered in particular to the level detection of 28 gene products.
19. the described gene product of claim 18 comprises the expression level that detects its mRNA with quantifying PCR method.
20. the described quantifying PCR method of claim 18 is the mammary cancer postoperative flesh tissue with patient, tissue and paraffin-embedded tissue after fixing.
21. the described quantifying PCR method of claim 18 comprises the expression of the house-keeping gene of quantitative PCR detection is obtained the estimation of whole genetic expression background with geometric mean, be used for correction other target gene expression levels.
22. the described quantitative PCT method of claim 18 comprises that each gene selects many methods of primer is improved simultaneously detection sensitivity and safety for use.
23. the said prognosis prediction of claim 3 adopts the integrated risk index, the recurrence exponential calculates the recurrence prognosis of estimating patient.
24. the described resistance prediction of claim 5 is adopted the resistance exponential of the specific chemotherapy regimen of comprehensive resistance exponential sum to calculate and is estimated the resistance of patient to chemotherapy.
25. the described particular medication resistance of claim 24 exponential calculates the resistance prediction that includes but not limited to for the CAF Combination chemotherapy.
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Cited By (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN105861695A (en) * | 2016-05-11 | 2016-08-17 | 江苏省肿瘤医院 | Method and kit for detecting drug resistance in breast cancer cells |
| CN107430133A (en) * | 2015-02-27 | 2017-12-01 | 延世大学校产学协力团 | For determine Prognosis in Breast Cancer and whether use chemotherapy apparatus and method |
| CN110468205A (en) * | 2013-08-19 | 2019-11-19 | 拜恩科技诊断有限责任公司 | Method and kit for tumor cells subtype typing |
| CN113846159A (en) * | 2021-01-27 | 2021-12-28 | 北京百奥纳芯生物科技有限公司 | Special chip for detecting expression of breast cancer related gene |
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2010
- 2010-07-21 CN CN2010102324469A patent/CN102337327A/en active Pending
Cited By (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN110468205A (en) * | 2013-08-19 | 2019-11-19 | 拜恩科技诊断有限责任公司 | Method and kit for tumor cells subtype typing |
| CN107430133A (en) * | 2015-02-27 | 2017-12-01 | 延世大学校产学协力团 | For determine Prognosis in Breast Cancer and whether use chemotherapy apparatus and method |
| CN105861695A (en) * | 2016-05-11 | 2016-08-17 | 江苏省肿瘤医院 | Method and kit for detecting drug resistance in breast cancer cells |
| CN113846159A (en) * | 2021-01-27 | 2021-12-28 | 北京百奥纳芯生物科技有限公司 | Special chip for detecting expression of breast cancer related gene |
| CN113846159B (en) * | 2021-01-27 | 2023-04-07 | 北京百奥纳芯生物科技有限公司 | Special chip for detecting expression of breast cancer related gene |
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